Ovarian cancer represents the third most frequent cancer and is one of the leading causes of cancer death among females in the United States and Europe (Gentry-Maharaj A, Menon U. Screening for ovarian cancer in the general population. Best Pract Res Clin Obstet Gynaecol. 2012; 26(2):243-256 PMID: 22182415; Schwartz P E, Taylor, K. J. Is early detection of ovarian cancer possible? Ann Med. 1995; 27:519-528; Bandera C A, Ye B, Mok S C. New technologies for the identification of markers for early detection of ovarian cancer. Curr Opin Obstet Gynecol. 2003; 15:51-55.). Most symptoms of ovarian cancer are vague and similar to those often experienced with more common, non-life-threatening health conditions. These symptoms might include abdominal swelling or bloating, pelvic pain or discomfort, lower back pain, loss of appetite or feeling full quickly, persistent indigestion, gas or nausea and changes in bowel or bladder habits. As a result, almost 80% of ovarian cancer patients are diagnosed at later stages. Unfortunately, the 5-year survival rate for patients with clinically advanced ovarian cancer is only 15% to 20%, in striking contrast to over 90% of 5-year survival rate for patients with stage I disease.
Currently, carcinoma antigen (CA)-125 and imaging are the two most common approaches for ovarian cancer screening tests. However, this marker has not proven useful for screening or diagnostic purposes due to low specificity and/or sensitivity. For example, serum CA-125 has been shown to have a sensitivity of greater than 98% but a specificity of only 50-60% for early-stage disease (Lowe K A, Shah C, Wallace E, Anderson G, Paley P, McIntosh M, et al. Effects of personal characteristics on serum CA125, mesothelin, and HE4 levels in healthy postmenopausal women at high-risk for ovarian cancer. Cancer Epidemiol Biomarkers Prev. 2008; 17:2480-2487; Badgwell, D. and Bast, R. C., Early detection of ovarian cancer. Dis Markers 2007; 23:397-410; Jacobs, I. J. and Menon, U. Progress and challenges in screening for early detection of ovarian cancer. Mol Cell Proteomics. 2004; 3, 355-366).
Multiple reports have identified serum ovarian cancer biomarkers using multiplex antibody array technology (Gorelik E, Landsittel D P, Marrangoni A M, Modugno F, Velikokhatnaya L, Winans M T, et al. Multiplexed immunobead-based cytokine profiling for early detection of ovarian cancer. Cancer Epidemiol Biomarkers Prev. 2005; 14(4):981-987; Mor G, Visintin I, Lai Y, Zhao H, Schwartz P, Rutherford T, et al. Serum protein markers for early detection of ovarian cancer. Proc Natl Acad Sci USA. 2005; 102(21):7677-7682; PMID: 15890779; Huang R, Jiang W, Yang J, Mao Y Q, Zhang Y, Yang W, et al. A biotin label-based antibody array for high-content profiling of protein expression. Cancer Genomics Proteomics. 2010; 7(3):129-141; PMID: 20551245.). One report identified a group of 6 serum protein markers, including IL-6, IL-8, epidermal growth factor (EGF), vascular endothelial growth factors (VEGF), monocyte chemoattractant protein-1 (MCP-1), and CA-125, which displayed significant difference in serum concentrations between ovarian cancer and control groups with 84% sensitivity at 95% specificity (Gorelik E, Landsittel D P, Marrangoni A M, Modugno F, Velikokhatnaya L, Winans M T, et al. Multiplexed immunobead-based cytokine profiling for early detection of ovarian cancer. Cancer Epidemiol Biomarkers Prev. 2005; 14(4):981-987). Another report identified a panel of 6 biomarkers (CA-125, OPN, IGF-II, MIF, Leptin and Prolactin) with a sensitivity of 95.3% and a specificity of 99.4% for the detection of ovarian cancer (Mor G, Visintin I, Lai Y, Zhao H, Schwartz P, Rutherford T, et al. Serum protein markers for early detection of ovarian cancer. Proc Natl Acad Sci USA. 2005; 102(21):7677-7682. PMID: 15890779). A 6-marker panel of proteins (IL-2 receptor-α, endothelin, osteprotegerin, vascular endothelial growth factor D (VEGF-D) and betacellulin (BTC)) was used to distinguish ovarian cancer patients from normal subjects (Huang R, Jiang W, Yang J, Mao Y Q, Zhang Y, Yang W, et al. A biotin, label-based antibody array for high-content profiling of protein expression. Cancer Genomics Proteomics. 2010; 7(3):129-141. PMID: 20551245.).
However, there remains an exigent need to discover and develop biomarkers for ovarian cancer screening and early detection.